Details

Details

Title Randomized Phase II Study of Cisplatin and Etoposide versus Temozolomide and Capecitabine in Patients with Advanced G3 Non-Small Cell Gastroenteropancreatic Neuroendocrine Carcinomas

IRB EA2142

CC 16-073

Hospital Fairview, Hillcrest, Independence, Main Campus, Mansfield, North Coast Cancer, South Pointe, Strongsville, Wooster

Phase Phase 2

Disease Pancreas

Drug Capecitabine, Cisplatin, Etoposide, Temozolomide

Description

Description

Primary Objectives
  • To assess the progression free survival (PFS) of cisplatin and etoposide versus the PFS of temozolomide and capecitabine in patients with advanced G3 non-small cell gastroenteropancreatic neuroendocrine carcinomas.
Secondary Objectives
  • To assess the response rate (RR) of cisplatin and etoposide versus the RR of temozolomide and capecitabine in patients with advanced G3 non-small cell gastroenteropancreatic neuroendocrine carcinomas.
  • To assess the overall survival (OS) of cisplatin and etoposide versus the OS of temozolomide and capecitabine in patients with advanced G3 non-small cell gastroenteropancreatic neuroendocrine carcinomas.
  • To evaluate the toxicities associated with the combination of temozolomide and capecitabine and the combination of cisplatin and etoposide, respectively, in patients with advanced G3 non-small cell gastroenteropancreatic neuroendocrine carcinomas.
Laboratory Research Objectives
  • To assess the impact of each treatment regimen on PFS, RR and OS based on Ki-67 index in patients with advanced G3 non-small cell gastroenteropancreatic neuroendocrine carcinomas.
  • To assess the prognostic significance of well differentiated versus poorly differentiated non-small cell gastroenteropancreatic neuroendocrine tumors in relationship to survival and response to treatment.
  • To assess the agreement in Ki-67 status between that reported by institutional pathologist and that reported by central pathology review.
Inclusion Criteria

Inclusion Criteria

  1. Patients must have a locally advanced and unresectable or metastatic gastroenteropancreatic neuroendocrine carcinoma of the GI tract.
  2. Patients must have pathologically/histologically confirmed tumor of non-small cell histology.
  3. Patients must have a Ki-67 proliferative index of 20-100%
  4. Patients must have evidence of at least 10 mitotic figures per 10 high powered fields.
  5. Patients must have measurable disease by RECIST 1.1 criteria as defined in Section 6.1.2. Baseline measurements and evaluations of all sites of disease must be obtained within 4 weeks prior to randomization and must be acquired by multiphasic CT or contrast MRI. NOTE: PET-CT scans are allowed provided the CT portion of the exam is equivalent to a diagnostic CT scan and includes both oral and IV contrast.
  6. Patients may not have had any prior treatment for this malignancy.
  7. Patients may not have received any of the protocol agents within 5 years prior to randomization.
  8. Any prior surgeries must have been completed at least 4 weeks prior to randomization.
  9. Patients must be at least ≥ 18 years of age.
  10. Patients must have an ECOG performance status of 0-2.
  11. Patients may not be receiving any other investigational agents while on study treatment.
  12. Patients may not be receiving Coumadin while on treatment. Other anticoagulants are allowed.
  13. Patients must have normal organ and marrow function as defined below within less than or equal to 14 days prior to randomization:
    • Leukocytes ≥ 3,000/mm3
    • Absolute neutrophil count ≥ 1,500/mm3
    • Hemoglobin ≥ 9 g/dL
    • Platelets ≥ 100,000/mm3
    • Total bilirubin ≤ institutional upper limit of normal (ULN) or ≤ 1.5 X institutional ULN (if the patient has liver metastases).
    • AST (SGOT)/ALT (SGPT) ≤ 2.5 X institutional ULN or (≤ 5 X institutional ULN if the patient has liver metastases).
    • Serum creatinine ≤ 1.5 X institutional ULN and creatinine clearance ≥ 60 ml/min NOTE: Creatinine Clearance must be calculated using the Cockcroft-Gault equation.
  14. Patients must have a life expectancy of ≥ 12 weeks as determined clinically by the treating physician.
  15. Patients with brain metastases (either remote or current) or presence of carcinomatous meningitis are not eligible
  16. Patients with known DPD deficiency will be excluded as the use of capecitabine is contraindicated in these patients.
  17. Patients must NOT have active or uncontrolled infection, symptomatic heart failure, unstable angina pectoris, cardiac arrhythmia or a serious psychiatric illness/social situation that would limit compliance with study requirements.
  18. Patients with impaired decision making capacity may participate in the study if a legal authorized representative is available to consent
  19. Patients must NOT have a history of allergic reactions attributed to compounds of similar chemical or biochemical composition to cisplatin, etoposide, temozolomide or capecitabine.
  20. Patients must NOT have absorption issues that would limit the ability to absorb study agents.
  21. Patients with a history of the following within ≤ 12 months of study entry are not eligible:
  22. Patients with symptomatic peripheral vascular disease are not eligible.
  23. Patients must NOT have previous or concurrent malignancy. Exceptions are made for patients who meet any of the following conditions:
    • Non-melanoma skin cancer, in situ cervical cancer, superficial bladder cancer, or breast cancer in situ. OR
    • Prior malignancy completely excised or removed and patient has been continuously disease free for > 5 years. OR
    • Prior malignancy cured by non-surgical modalities and patient has been continuously disease free for > 5 years.
  24. Women must not be pregnant or breast-feeding due to potential harm to the fetus from cisplatin, etoposide, temozolomide and/or capecitabine. All females of childbearing potential must have a blood test or urine study within 2 weeks prior to randomization to rule out pregnancy. A female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
  25. Women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective method of contraception or to abstain from sexual intercourse for the duration of their participation in the study.
  26. Patients must be able to swallow pills.
  27. Patients must be able to tolerate CT or MR imaging including contrast agents as required for the treatment and the protocol.
  28. Patients who are known to have HIV or are on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with cisplatin, etoposide, temozolomide, and/or capecitabine. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
Exclusion Criteria

Exclusion Criteria

Exclusion Criteria Not Available